RGD Reference Report - Peroxisome proliferator-activated receptor-alpha agonists protect cortical neurons from inflammatory mediators and improve peroxisomal function. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Peroxisome proliferator-activated receptor-alpha agonists protect cortical neurons from inflammatory mediators and improve peroxisomal function.

Authors: Gray, E  Ginty, M  Kemp, K  Scolding, N  Wilkins, A 
Citation: Gray E, etal., Eur J Neurosci. 2011 Apr;33(8):1421-32. doi: 10.1111/j.1460-9568.2011.07637.x. Epub 2011 Mar 7.
RGD ID: 8693656
Pubmed: PMID:21375604   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1460-9568.2011.07637.x   (Journal Full-text)

Inflammation is known to cause significant neuronal damage and axonal injury in many neurological disorders. Among the range of inflammatory mediators, nitric oxide is a potent neurotoxic agent. Recent evidence has suggested that cellular peroxisomes may be important in protecting neurons from inflammatory damage. To assess the influence of peroxisomal activation on nitric oxide-mediated neurotoxicity, we investigated the effects of the peroxisomal proliferator-activated receptor (PPAR)-alpha agonist fenofibrate on cortical neurons exposed to a nitric oxide donor or co-cultured with activated microglia. Fenofibrate protected neurons and axons against both nitric oxide donor-induced and microglia-derived nitric oxide-induced toxicity. Moreover, cortical neurons treated with this compound showed a significant increase in gene expression of ABCD3 (the gene encoding for peroxisomal membrane protein-70), with a concomitant increase in protein levels of PPAR-alpha and catalase, which was associated with a functional increase in the activity of this enzyme. Collectively, these observations provide evidence that modulation of PPAR-alpha activity and peroxisomal function by fenofibrate attenuates nitric oxide-mediated neuronal and axonal damage, suggesting a new therapeutic approach to protect against neurodegenerative changes associated with neuroinflammation.

Objects referenced in this article
Gene Ppara peroxisome proliferator activated receptor alpha Rattus norvegicus

Additional Information